1. Field of the Invention
This invention relates to antibacterial chemical compounds of the type called cephalosporins and particularly to a chemical method of purifying a particular cephalosporin.
2. Description of the Prior Art
7-[.alpha.-(2-Aminomethylphenyl)acetamido]-3-[(1-carboxymethyltetrazol-5-yl thio)methyl]-3-cephem-4-carboxylic acid, for which the U.S. Adopted Name is ceforanide, is also sometimes referred to here and in the literature as BL-S786. For publications on ceforanide see, for example, Leitner et al., Laboratory Evaluation of BL-S786, a Cephalsoporin with Broad-Spectrum Antibacterial Activity, Antimicrobial Agents and chemotherapy, 10(3), 426-435 (Sept. 1976) and Gottstein et al., J. Antibiotics, 29(11), 1226-1229 (1976) and U.S. Pat. No. 4,100,346 (July, 1978). Gottstein et al. used trace amounts of N,N-dimethylbenzylamine as an acid-scavenging agent during preparation of the mixed anhydride of the side chain acid and larger amounts of N-methylmorpholine to dissolve the 3-thiolated-7-aminocephalosporanic acid prior to acylation.
The amines first used with benzylpenicillin have also been disclosed (in general terms and with no information as to solubility) to be capable of forming salts with the acidic carboxyl of cephalosporins including ceforanide (see U.S. Pat. No. 4,100,346). These amines include trialkylamines such as triethylamine, procaine, dibenzylamine, N-benzyl-.beta.-phenethylamine, 1-ephenamine, N,N'-dibenzylethylenediamine, dehydroabietylamine, N,N'-bis-dehydroabietylethylenediamine, and N-(lower)alkylpiperidines such as N-ethylpiperidine; see for example U.S. Pat. Nos. 3,488,730; 3,634,416 (collidine); 3,634,417 (benzylamine); 3,766,175 (which also reviews earlier literature); 3,830,809 (dicyclohexylamine); 3,907,786; 3,946,000 and U.K. Pat. No. 1,265,315 and Farmdoc 79940X (dibenzylamine) and Farmdoc 11639X (N,N'-dibenzylethylenediamine).
For salts or complexes with aminoacids such as lysine, histidine or arginine with other cephalosporins see Farmdoc 66666V and 95117X and U.S. Pat. No. 3,984,403 and U.K. Pat. No. 1,460,327 and with BL-S786 see Research Disclosure, 157, 75-76 (May, 1977).
As used below BDMA means benzyldimethylamine which is also named as N,N-dimethylbenzylamine.